title: Aflibercept-mediated early angiogenic changes in aggressive B-cell lymphoma.
abstract: OBJECTIVE
  Diffuse large B-cell lymphoma is the most common and one of the most aggressive lymphomas in adults. The standard, R-CHOP-based treatment needs improvement. There has been recent interest in anti-angiogenic therapy, but its cellular effects in lymphoma are little known.
  
  
  METHODS
  In five aggressive B-cell lymphoma patients, we analyzed the microvessel and lymphoma cell changes after Aflibercept, an angiogenic inhibitor. Under ultrasonography, we performed two biopsies, one before any treatment and one two hours after Aflibercept, before R-CHOP. Using ultrasonography, immuno-histochemistry, double immuno-fluorescent staining, and electron microscopy, we compared the early changes induced by Aflibercept to the early changes induced by R-CHOP in three control patients.
  
  
  RESULTS
  We identified microvessel damage in the five patients treated with Aflibercept but not in the three patients treated with R-CHOP. Two hours after Aflibercept, microvessel damage was focal, with severely damaged microvessel sections close to normal ones in the same area; different stages of microvessel damage were concomitantly found, with an increase in relative necrosis area in three cases. There was no difference in necrosis or relative microvessel area after R-CHOP. For lymphoma cells, the two biotherapies induced similar changes, with increase in apoptosis but not in proliferation.
  
  
  CONCLUSIONS
  We identified focal microvascular damage, necrosis, and apoptosis of lymphoma cells in aggressive B-cell lymphoma as soon as 2 h after Aflibercept. This suggests that there is more than one mechanism associated with the early effect of anti-angiogenic therapy in lymphoma.
authors.affiliation: Laboratoire de Pathologie, U728, AP-HP-Hôpital Saint-Louis, 1, Avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Martha
authors.initials: M
authors.lastname: Romero
authors.forename: Josette
authors.initials: J
authors.lastname: Brière
authors.forename: Cédric
authors.initials: C
authors.lastname: de Bazelaire
authors.forename: Christophe
authors.initials: C
authors.lastname: Lebœuf
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Philippe
authors.initials: P
authors.lastname: Ratajczak
authors.forename: David
authors.initials: D
authors.lastname: Sibon
authors.forename: Eric
authors.initials: E
authors.lastname: de Kerviler
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D014463:Ultrasonography
chemical_list: D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor